The genus Sacosperma (Rubiaceae) comprises two species of lianas occurring in tropical African rainforests. It is currently placed in tribe Spermacoceae, but morphological evidence suggests that placement in tribe Knoxieae might be more appropriate. This study presents the first molecular analysis of Sacosperma, which supports its placement within Knoxieae, where it is sister to the East African genus Rhodopentas. A close relationship between these two genera has never been considered before, and molecular data alone cannot resolve whether they should be treated as distinct genera. To address this, we provide a comparative analysis of Sacosperma and Rhodopentas based on morphology, anatomy, biogeography, and climate preference. The recognition of Sacosperma and Rhodopentas as two separate genera is justified, given a number of morphological differences (e.g., habit, imperforate tracheary elements, domatia, stipules, inflorescences, flower size and color), their biogeography (West and Central African vs. East African), and climate preferences (broad vs. narrow climate envelope). Sacosperma and Rhodopentas share a common ancestor that has likely diverged morphologically in response to differing ecological conditions.